Abstract: :
Purpose:Msx2, a homeodomain transcriptional factor belongingto the msh gene family, has been shown to be expressed in thedeveloping optic vesicle. The aim of this study was to investigatepossible function of Msx2 in controlling retinal ganglion cell(RGC) development.Methods: For this investigation, we utilized transgenic animalsthat overexpress Msx2. Msx2 transgenic embryos or adult andnontransgenic littermates were examined histopathologically.To follow RGC development, the expression of RGC–specificmarkers was assessed by performing in situ hybridization orimmunohistochemical staining.Results: Forced expression of the Msx2 gene resulted in RGCdeficiency. At E12.5, differentiation of RGC has occurred inthe nontransgenic neural retina as RGCs sent axonal projectionsmedially though the optic stack. However, in the Msx2 transgenicretina, RGC differentiation did not occur at the same developmentalstage. At E12.5, the expression of Math5 and Brn3b, two RGCearly differentiation markers, didn’t appear in the transgenicmice retina while they were expressed in the retina of the wildlittermate. However, at E15, Math5 and Brn3b were expressedin the transgenic mice retina, though the expression domainin the developing retina was, to some extent, different fromthat in the wild littermate. In the adult transgenic retina,neural retina survived but a large reduction in cell numberof RGC layer was evident. The number of RGCs labeled by anti–Pax6antibody was reduced remarkably in the RGC layer of the transgenicretina.Conclusions: These results indicated that forced expressionof the Msx2 gene delayed differentiation of RGCs and resultedin RGC deficiency.